The goals of the proposed plan are to train Dr. Cristina Llerena Law as a clinician scientist and independent patient based researcher and to develop and assess the value of theoretically motivated binocular treatments for amblyopia in adult humans. An asymmetry in the visual input across the eyes early in postnatal life causes amblyopia, the most common basis of monocular visual impairment in humans. If uncorrected, amblyopia results in the unaffected eye controlling the binocular visual cortex, while the ability f the affected eye to stimulate cortical neurons may weaken to the point of functional blindness. Previous attempts to recover vision in adult amblyopes have had limited success, and recent data suggest that binocular training techniques, which normalize neuronal responses across the two eyes, may enhance learning effects (Hess et al, 2010; Ding et al, 2006). The use of perceptual learning procedures with mixed-contrast stimuli may be ideally suited for vision training in adult amblyopes, where limitations in synaptic plasticity in visual cortex may prevent conventional monocular training techniques from being effective. Recent work has established new methods for measuring inter-ocular contrast ratios (ICR) that provide balanced inputs, between the two eyes, during binocular vision (Mansouri et al, 2008; Huang et al, 2009). We will assess the validity of these established methods and design our own protocols for measuring this parameter. We will then exploit this symmetric sensory input during binocular training in adult amblyopes using both new and established perceptual learning procedures. We believe that techniques which harness the use of binocularity and equal sensory input between the two eyes may provide enhanced recovery of visual function in adult amblyopes, which would promise new non-invasive treatments of adult amblyopia. The proposed work will make use of magnetoencephalography (MEG) both to measure responses from the amblyopic eye, and for the first time, to measure binocular interactions using dichoptic mixed temporal-frequency stimuli similar to stimuli used previously with VEP/EEG. Dr. Llerena Law has assembled a team of mentors, collaborators, and consultants to provide her with the best tools to make a transition into independent patient based research. This team has also been ideally assembled to provide Dr. Law with the resources and skills to test this hypothesis, using a comprehensive analysis of visual functions, including psychophysics and physiology, and to track changes in visual function at key milestones during the experiment. If successful, this work would transform therapy for adult amblyopia, and focus attention on the importance of incorporating methods to reduce suppression. In addition, the insight gained from this work could be extended to strabismus, eye movement control disorders, and the restoration of optimal neural function after damage from traumatic brain injury. PUBLIC HEALTH RELEVANCE: Attempts to restore visual acuity in adults with amblyopia have had limited success, presumably due to constraints on synaptic plasticity in the adult visual system. We propose to use binocular methods during perceptual learning to normalize neuronal responses across the two eyes. We propose that this approach will enhance the recovery of visual function through training with perceptual learning. If this approach is successful, binocula perceptual learning methods that target suppression could be used as a clinical tool to make amblyopia treatments more effective in adults.